Mechanisms of bone cancer pain

骨癌疼痛的机制

• 批准号: 16390455
• 负责人: NAMIKI Akiyoshi
• 金额: $ 8.9万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390455/
• 关键词: TRPV1; mu opioid receptor; bone cancer; cancer pain; immunohistochemistry; mRNA; CGRP; IB4; 疼痛; オピオイド; 後根神経節; 脊髄; 炎症; CGRP; 癌性疼痛; 骨癌; エンドセリン; カプサイシン受容体; 骨癌性疼痛; 脊髄後根神経節; 疼痛関連行動; 骨破壊; Western blot法

Although mu opioid receptor (MOR) agonists are used in treating most type of pain, a recent study suggested that the sensitivity of bone cancer pain to morphine was lower than that of inflammatory pain. However, the reasons for this have remained unclear. In this study, MOR expression and the analgesic effects of morphine in a bone cancer model were compared with those in an inflammatory pain model. A bone cancer pain model and an inflammatory pain model were made by injection of sarcoma cells into the intramedullary space of the femur and hindpaw injection of complete Freund's adjuvant (CFA), respectively. In behavioral study, mice with sarcoma injection showed flinching behavior of comparable magnitude induced by CFA-induced inflammation. Both intraperitoneal and intrathecal morphine was less effective on flinching behavior of mice with bone cancer than that of mice with CFA injection. Western blot analysis showed that MOR expression in dorsal root ganglion (DRG) ipsilateral to sarcoma injection was significantly reduced, while that ipsilateral to CFA injection was increased. In mice with sarcoma injection, the percentage of MOR-positive DRG neurons was lower than that in control mice (30.3% vs. 45.2%, respectively). In particular, MOR expression was reduced among CGRP- and TRPV1-positive DRG neurons, which are believed to be nociceptive (from 61.5% to 41.5% and from 72.1% to 48.4%, respectively). These results suggest that down-regulation of MOR in a distinct population of DRG neurons contribute to the relative inefficacy of morphine in treating bone cancer pain.

尽管Mu阿片受体激动剂被用于治疗大多数类型的疼痛，但最近的一项研究表明，骨癌疼痛对吗啡的敏感性低于炎症性疼痛。然而，造成这种情况的原因尚不清楚。在这项研究中，比较了骨癌模型和炎性疼痛模型中MOR的表达和吗啡的止痛效果。分别采用股骨髓内注射肉瘤细胞和足底注射弗氏完全佐剂(CFA)的方法制作骨癌痛模型和炎性疼痛模型。在行为学研究中，注射肉瘤的小鼠表现出与CFA诱导的炎症类似程度的退缩行为。腹腔注射和鞘内注射吗啡对骨癌小鼠的退缩行为的影响均弱于注射CFA的小鼠。Western印迹分析显示，肉瘤注射同侧背根神经节(DRG)中MOR的表达显著降低，而CFA注射同侧背根神经节(DRG)中MOR的表达明显增加。肉瘤注射组小鼠背根神经节MOR阳性神经元的百分比低于对照组(分别为30.3%和45.2%)。特别是，在被认为是伤害性感受的CGRP和TRPV1阳性的DRG神经元中，MOR的表达减少(分别从61.5%到41.5%和72.1%到48.4%)。这些结果表明，在不同的DRG神经元群体中，MOR的下调是吗啡治疗骨癌疼痛相对无效的原因之一。

项目成果

Role of Prostaglandin Receptor Subtype EP_1 in Prostaglandin E_2-induced nociceptive transmission in the rat spinal dorsal horn.

前列腺素受体亚型 EP_1 在前列腺素 E_2 诱导的大鼠脊髓背角伤害性传递中的作用。

• 发表时间: 2004
• 期刊: Brain Research 1010
• 作者: Nakayama Y;Omote K
• 通讯作者: Omote K

Use of percutaneous cardiopulmonary support in catastrophic massive pulmonary fat embolism.

经皮心肺支持在灾难性的大量肺脂肪栓塞中的应用。

• 发表时间: 2006
• 期刊: Br J Anaesth 96
• 作者: Hirasawa H;Sakai A;Nakamura T;et. al.;Kawamata T;Kawamata M;Iwasaki S;Kawamata M.;Igarashi M.
• 通讯作者: Igarashi M.

Effects of halothane and isoflurane on hyperexcitability of spinal dorsal horn neurons after incision in the rat.

氟烷和异氟烷对大鼠切口后脊髓背角神经元过度兴奋的影响。

• 发表时间: 2005
• 期刊: Anesthesiology 102
• 作者: Kawamata M;Narimatsu E;Kozuka Y;Takahashi T;Sugino S;Niiya T;Namiki A.
• 通讯作者: Namiki A.

Effects of systemic administration of lidocaine and QX-314 on hyperexcitability of spinal dorsal horn neurons after incision in the rat

• DOI: 10.1016/j.pain.2006.01.004
• 发表时间: 2006-05-01
• 期刊: PAIN
• 影响因子: 7.4
• 作者: Kawamata, Mikito;Sugino, Shigekazu;Namiki, Akiyoshi
• 通讯作者: Namiki, Akiyoshi

The addition of epidural morphine to ropivacaine improves epidural analgesia after lower abdominal surgery

罗哌卡因中加入硬膜外吗啡改善下腹部手术后硬膜外镇痛

• 发表时间: 2005
• 期刊: Canadian Journal of Anaesthesia 52
• 作者: Omae T;Kakihana Y;Matsunaga A;Tsuneyoshi I;Kawasaki K;Kanmura Y;Sakata R;垣花泰之;Yamamoto H;Niiyama Y
• 通讯作者: Niiyama Y